NCT03714555

Brief Summary

This is an open-label Phase 2 Pilot study to evaluate Disulfiram + Copper Gluconate in patients metastatic pancreatic cancer whose CA-19-9 levels rise while receiving nab-paclitaxel (Abraxane) plus gemcitabine (Gemzar) or FOLFIRINOX or single-agent gemcitabine (Gemzar). Patient must have received a minimum of 8 weeks of treatment and have rising CA-19-9 levels in the absence of radiographic evidence of progression.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Oct 2019

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 9, 2018

Completed
13 days until next milestone

First Posted

Study publicly available on registry

October 22, 2018

Completed
12 months until next milestone

Study Start

First participant enrolled

October 17, 2019

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 22, 2020

Completed
7 days until next milestone

Study Completion

Last participant's last visit for all outcomes

July 29, 2020

Completed
3.2 years until next milestone

Results Posted

Study results publicly available

October 18, 2023

Completed
Last Updated

October 18, 2023

Status Verified

September 1, 2023

Enrollment Period

9 months

First QC Date

October 9, 2018

Results QC Date

August 24, 2023

Last Update Submit

September 26, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • CA19-9 Plasma Level

    Change in plasma CA19-9 level (at least 30%) from baseline

    From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (9)

  • Complete Tumor Response

    From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  • Partial Response

    From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  • Stable Disease

    From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  • Overall Response Rate

    From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  • Overall Survival

    From date of enrollment until date of death assessed up to 100 months

  • +4 more secondary outcomes

Other Outcomes (1)

  • Disulfiram/Copper Gluconate Serum Levels - Area Under the Curve (AUC)

    Day 0 (pre-Cycle 1 Day 1) at pre-dose, 2 hours, 4 hours, 24 hours and 4 hours post-dose Cycle 1 Day 7

Study Arms (3)

Nab-Paclitaxel/Gemcitabine + DSF/Cu

ACTIVE COMPARATOR

Subjects with metastatic adenocarcinoma of the pancreas who have received a minimum of 8 weeks of treatment with Nab-Paclitaxel-Gemcitabine with rising CA 19-9 levels in the absence of radiographic evidence of progression will continue to receive treatment with addition of Disulfiram+Copper Gluconate until disease progression.

Diagnostic Test: Safety LaboratoriesOther: AE AssessmentOther: Physical ExamOther: Concomitant Medication ReviewDiagnostic Test: Tumor ImagingDrug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper GluconateDrug: FOLFIRINOX regimen Plus Disulfiram/Copper GluconateDrug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate

FOLFIRINOX +DSF/Cu

ACTIVE COMPARATOR

Subjects with metastatic adenocarcinoma of the pancreas who have received a minimum of 8 weeks of treatment with FOLFIRINOX and with rising CA 19-9 levels in the absence of radiographic evidence of progression will continue to receive treatment with addition of Disulfiram+Copper Gluconate until disease progression.

Diagnostic Test: Safety LaboratoriesOther: AE AssessmentOther: Physical ExamOther: Concomitant Medication ReviewDiagnostic Test: Tumor ImagingDrug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper GluconateDrug: FOLFIRINOX regimen Plus Disulfiram/Copper GluconateDrug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate

Single-Agent Gemcitabine +DSF/Cu

ACTIVE COMPARATOR

Subjects with metastatic adenocarcinoma of the pancreas who have received a minimum of 8 weeks of treatment with Single-Agent Gemcitabine and with rising CA 19-9 levels in the absence of radiographic evidence of progression will continue to receive treatment with addition of Disulfiram+Copper Gluconate until disease progression.

Diagnostic Test: Safety LaboratoriesOther: AE AssessmentOther: Physical ExamOther: Concomitant Medication ReviewDiagnostic Test: Tumor ImagingDrug: nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) Protocol Plus Disulfiram/Copper GluconateDrug: FOLFIRINOX regimen Plus Disulfiram/Copper GluconateDrug: Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate

Interventions

Safety LaboratoriesDIAGNOSTIC_TEST

Complete blood cell count (CBC) w Differential, comprehensive metabolic panel (CMP), Prothrombin time/international normalized ratio (PT/INR) Activated Partial Thromboplastin Time (aPTT), Urinalysis

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

Assessment of Adverse Events (AE)

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

Physical Exam, Weight, Vital Signs, Eastern Cooperative Oncology Group (ECOG) Performance Status

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

Prior and Concomitant Medication Review

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu
Tumor ImagingDIAGNOSTIC_TEST

Tumor CT or MRI

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

nab-paclitaxel (Abraxane)/gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

FOLFIRINOX regimen Plus Disulfiram/Copper Gluconate dispensing

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

Single-agent gemcitabine (Gemzar) regimen Plus Disulfiram/Copper Gluconate dispensing

FOLFIRINOX +DSF/CuNab-Paclitaxel/Gemcitabine + DSF/CuSingle-Agent Gemcitabine +DSF/Cu

Eligibility Criteria

Age18 Years - 105 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have histologically confirmed adenocarcinoma of the pancreas that is metastatic and for which potential curative measures, such as resection of an isolated metastasis, are not available. Patients with islet cell neoplasms are excluded.
  • Patient should currently be receiving a chemotherapy regimen comprising FOLFIRINOX or Abraxane-Gemcitabine or single-agent Gemcitabine as front-line treatment for metastatic disease. Patients who have had chemotherapy in the adjuvant or neoadjuvant setting are eligible.
  • Patients must have previously received a minimum of 8 weeks of therapy with Abraxane-Gemcitabine or FOLFIRINOX or single-agent Gemcitabine without radiographic evidence of disease progression based on the investigator's opinion, but a rising CA 19-9 level, and still be undergoing treatment with Abraxane-Gemcitabine or FOLFIRINOX or single-agent Gemcitabine. Increased CA 19-9 is defined as an increased over baseline of \> 20% in two consecutive time points within 8 days of each other.
  • Patient has one or more metastatic tumors measurable by CT scan. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>20 mm with conventional techniques or as \>10 mm with spiral CT scan.
  • Male or non-pregnant and non-lactating female and ≥ 18 to ≤ 80 years of age.
  • Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count ≥ 100,000/mm3 (100 × 109/L); Hemoglobin (Hgb) ≥ 9 g/dL.
  • Patient has the following blood chemistry levels at Screening (obtained ≤ 14 days prior to enrollment) and at Baseline-Day 0:
  • aspartate aminotransferase (AST) (SGOT), Alanine Transaminase (ALT) (SGPT) ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 × ULN is allowed. Total bilirubin ≤ 1.5 × ULN.
  • Serum creatinine \< 1.5X ULN or estimated creatinine clearance of \> 60 mL/min (per Cockroft-Gault formula)
  • Patient has ECOG performance status from 0 to ≤ 1.
  • Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.

You may not qualify if:

  • Patient has brain metastases.
  • Patient has experienced an increase of ECOG to \> 1 between Screening and enrollment.
  • QTc \> 480 msec if patient receiving oxaliplatin-containing regimen.
  • Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
  • Patient has a history of allergy or hypersensitivity to any of the study drugs, their pharmaceutical class or any of their excipients. The patient exhibits any of the events outlined in the Contraindications or Special Warnings and Precautions sections of Gemcitabine or Abraxane ® Prescribing Information package inserts or on the Investigator's Brochure for DSF/Cu.
  • Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity.
  • Patient is enrolled in any other clinical protocol or investigational trial involving administration of antineoplastic compounds for the treatment of metastatic pancreatic cancer.
  • Patient is unwilling or unable to comply with study procedures.
  • Abraxane is metabolized by CYP2C8 and CYP3A4. Co-administration of substrates, inhibitors of CYP2C8 (see Appendix C) and/or CYP3A4 (see Appendix D) with Abraxane is not allowed. The following medications and substances are not allowed during the study: ritonavir, saquinavir, indinavir, nelfinavir, rifampicin, carbamazepine, phenytoin, efiravenz, or nerivapine, grapefruit (juice or seeds) or some herbals like St. John's wort.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

HonorHealth Research Institute

Scottsdale, Arizona, 85251, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Restraint, Physical130-nm albumin-bound paclitaxelGemcitabineClinical ProtocolsDisulfiramGluconates

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

Behavior ControlTherapeuticsImmobilizationInvestigative TechniquesHeterocyclic CompoundsDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingEpidemiologic Study CharacteristicsHealth Care Evaluation MechanismsQuality of Health CareHealth Care Quality, Access, and EvaluationDitiocarbThiocarbamatesCarbamatesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsDisulfidesSulfidesSulfur CompoundsSugar AcidsHydroxy AcidsCarbohydrates

Results Point of Contact

Title
Gayle Jameson, MSN, ACNP-BC, AOCN
Organization
HonorHealth

Study Officials

  • Gayle Jameson, ACNP-BC

    HonorHealth Research Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 9, 2018

First Posted

October 22, 2018

Study Start

October 17, 2019

Primary Completion

July 22, 2020

Study Completion

July 29, 2020

Last Updated

October 18, 2023

Results First Posted

October 18, 2023

Record last verified: 2023-09

Data Sharing

IPD Sharing
Will not share

Locations